tbuckley/cabot-search huggingface dataset:
Germline genetic variants and pediatric rhabdomyosarcoma outcomes: a report from the Children’s Oncology Group
Authors: Bailey A Martin-Giacalone, Melissa A Richard, Michael E Scheurer, Javed Khan, Pagna Sok, Priya B Shetty, Stephen J Chanock, Shengchao Alfred Li, Meredith Yeager, Deborah A Marquez-Do, Donald A Barkauskas, David Hall, Matthew T McEvoy, Austin L Brown, Aniko Sabo, Paul Scheet, Chad D Huff, Stephen X Skapek, Douglas S Hawkins, Rajkumar Venkatramani, Lisa Mirabello, Philip J Lupo
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Relative to other pediatric cancers, survival for rhabdomyosarcoma (RMS) has not improved in recent decades, suggesting the need to enhance risk stratification. Therefore, we conducted a genome-wide association study for event-free survival (EFS) and overall survival (OS) to identify genetic variants associated with outcomes in individuals with RMS. Methods The study included 920 individuals with newly diagnosed RMS who were enrolled in Children’s Oncology Group protocols. To assess the association of each single nucleotide polymorphism (SNP) with EFS and OS, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using multivariable Cox proportional hazards models, adjusted for clinical covariates. All statistical tests were two sided. We also performed stratified analyses by histological subtype (alveolar and embryonal RMS) and carried out sensitivity analyses of statistically significant SNPs by PAX3/7-FOXO1 fusion status and genetic ancestry group. Results We identified that rs17321084 was associated with worse EFS (HR = 2.01, 95% CI = 1.59 to 2.53, P = 5.39 × 10−9) and rs10094840 was associated with worse OS (HR = 1.84, 95% CI = 1.48 to 2.27, P = 2.13 × 10−8). Using publicly available data, we found that rs17321084 lies in a binding region for transcription factors GATA2 and GATA3, and rs10094840 is associated with SPAG1 and RNF19A expression. We also identified that CTNNA3 rs2135732 (HR = 3.75, 95% CI = 2.34 to 5.99, P = 3.54 × 10−8) and MED31 rs74504320 (HR = 3.21, 95% CI = 2.12 to 4.86, P = 3.60 × 10−8) were associated with worse OS among individuals with alveolar RMS. Conclusions We demonstrated that common germline variants are associated with EFS and OS among individuals with RMS. Additional replication and investigation of these SNP effects may further support their consideration in risk stratification protocols.
Accuracy of multidetector spiral computed tomography in identifying and differentiating the composition of coronary atherosclerotic plaques
Authors: Alexander W Leber, Andreas Knez, Alexander Becker, Christoph Becker, Franz von Ziegler, Konstantin Nikolaou, Carsten Rist, Maximilian Reiser, Carl White, Gerhard Steinbeck, Peter Boekstegers
Journal: Journal of the American College of Cardiology (2004)
LDH serum levels as a predictive factor for global outcome in pretreated colorectal cancer patients receiving regorafenib: Implications for clinical management.
Authors: Michela Del Prete, Mario Scartozzi, Tiziana Prochilo, Luca Faloppi, Riccardo Giampieri, Maristella Bianconi, Rossana Berardi, Azzurra Onofri, Alessandro Bittoni, Alberto Zaniboni, Stefano Cascinu
Journal: Journal of Clinical Oncology (2014)

497 Background: Although a demonstrated clinical efficacy, a non negligible proportion of colorectal cancer patients does not seem to benefit from regorafenib and are consequently exposed to unnecessary toxicity. LDH serum levels represent an indirect marker of tumour hypoxia, neo-angiogenesis and worse prognosis in many tumour types. In colorectal cancer LDH showed a correlation with treatment outcome for patients receiving antiangiogenetic treatment, thus suggesting a possible interaction with the activity profile of these drugs. We analyzed the role of LDH serum levels in predicting clinical outcome for pre-treated metastatic colorectal cancer patients receiving regorafenib. The final aim was to individuate a potentially reliable and easy to use marker for patients stratification. Methods: 118 colorectal cancer patients treated with regorafenib were available for our analysis. For all patients, LDH values were collected within one month before the procedure and after treatment end. LDH cutoff value was determined by ROC curve analysis, patients were then divided into two groups (A and B, below and above cut-off level respectively). Patients were also classified according to the variation in LDH serum levels pre- and post-treatment (increased patients vs. decreased patients). Results: Patients in group A and B proved homogeneous for all clinical characteristics analyzed. In group A patients median progression free survival (PFS) was 3.18 months, whereas it was 1.87 months in group B patients (p = 0.0018). Median overall survival (OS) was 6.23 months and 3.28 months in group A and B respectively (p = 0.048). Significant differences were not noted among the 2 groups for response rate. All the other clinical variables analyzed failed to show any correlation with patients outcome. Conclusions: Our observations seem to suggest a role of LDH as a marker of clinical outcome in colorectal cancer patients receiving regorafenib. We can then speculate that high LDH patients may not be optimal candidates for regorafenib. After further confirmation in larger trial, these findings may be relevant for a better patients stratification and selection.
A syndrome of depression and mutism in the Oglala Sioux
Authors: Thomas H. Lewis
Journal: American Journal of Psychiatry (1975)

The wacinko syndrome in the Oglala Sioux varies from a nonclinical reaction to pathological degrees of anger, pouting, withdrawal, depression, psychomotor retardation, mutism, immobility, and even to suicide. Although indigenous proctitioners recognize the syndrome as a distinctive disorder, it has not been described by non-Indian practitioners. The author presents a case report and suggests that most cases are diagnosable as reactive depressive illness.
Abstract 15762: Interleukin-1 Blockade Improves Cardiopulmonary Exercise Performance In Patients With Systolic Heart Failure
Authors: Benjamin W Van Tassell, Ross A Arena, Keyur Shah, Stefano Toldo, Eleonora Mezzaroma, Gihun Kim, Che M Chang, Bryan Yumori, Norbert F Voelkel, Antonio Abbate
Journal: Circulation (2011)

Background.  Heart failure (HF) is a complex clinical syndrome characterized by impaired cardiac function and poor exercise tolerance. Enhanced inflammation is associated with worsening outcomes in HF patients and may play a direct role in disease progression. Interleukin-1 (IL-1) is a pro-inflammatory cytokine that becomes chronically elevated in HF and exerts putative negative inotropic effects. We hypothesized that IL-1 blockade would improve exercise performance in patients with systolic HF and evidence of elevated inflammatory activity.   Methods.  We conducted a single-arm, open-label, pilot study (NCT01300650) of IL-1 blockade in HF patients (NYHA functional class II - III) with documented LVEF   Results.  All patients experienced numerical improvements in peak VO2 and exercise time. Mean peak VO2 increased from 12.95±1.03 to 16.25±1.01 mL/kg/min (+3.25 mL/kg/min, P   Conclusions.  IL-1 blockade with anakinra was associated with a significant improvement in peak VO2 in patients with systolic HF and elevated hsCRP. IL-1 blockade may represent a potential treatment modality to improve exercise capacity HF patients.
Nova et Vetera
Authors: W H ARMYTAGE
Journal: BMJ (1960)

The coffee-houses which began to proliferate after the Restoration incubated insurance companies, news-letters, societies, and clubs.They also provided doctors with opportunities to meet their patients, and apothecaries to obtain advice from the specialists of the day.Their role as seed-beds of science is also not without interest.From their very beginning this can be traced.Thus Arthur Tillyard, who established a coffee-house near All Saints', Oxford, in 1655, used to entertain Millington and Peter Pett, together with early members of the Royal Society.It was at Till- yard's that Peter Staehl taught chemistry until 1662 before migrating to London and Robert Boyle's laboratory.John
Abstract 1933: Aprotinin is Not Associated With Renal Failure or Increased Mortality in Children Undergoing Congenital Heart Surgery
Authors: Sara K Pasquali, Matthew Hall, Jennifer S Li, Eric D Peterson, James Jaggers, Andrew J Lodge, Jeffrey P Jacobs, Marshall L Jacobs, Samir S Shah
Journal: Circulation (2009)

Background: Aprotinin was used frequently in children undergoing congenital heart surgery until it was taken off the market in 2007 following studies demonstrating increased mortality and renal fai...
Abstract 3297: Combination of Coronary Artery Calcium and Carotid Artery Plaque Scores as a Powerful Negative Predictor for Coronary Artery Disease
Authors: Kumiko Konno, Naoyuki Yokoyama, Shigeru Suzuki, Yasunari Ueno, Ken Kozuma, Taiji Furukawa, Takaaki Isshiki
Journal: Circulation (2007)

Objective: Coronary artery calcium score (CACS) measured by MSCT, carotid plaque score (CPS) measured by carotid ultrasound, and brachial-ankle pulse wave velocity (baPWV) are noninvasive screening...
Variability in <i>MUC5B</i> Expression Is Dependent on Genotype and Endotype in Idiopathic Pulmonary Fibrosis
Authors: Auyon J. Ghosh, Matthew Moll, Brian D. Hobbs, Jonathan Cardwell, Aabida Saferali, Peter J. Castaldi, Michael H. Cho, Edwin K. Silverman, Ivana V. Yang, Craig P. Hersh
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Variability in MUC5B Expression Is Dependent on Genotype and Endotype in Idiopathic Pulmonary Fibrosis." American Journal of Respiratory and Critical Care Medicine, 207(10), pp. 1401–1404
Higher Neighborhood Drivability Is Associated With a Higher Diabetes Risk in Younger Adults: A Population-Based Cohort Study in Toronto, Canada
Authors: Nicolette R. den Braver, Joline W.J. Beulens, C. Fangyun Wu, Ghazal S. Fazli, Peter Gozdyra, Nicholas A. Howell, Jeroen Lakerveld, John S. Moin, Femke Rutters, Johannes Brug, Rahim Moineddin, Gillian L. Booth
Journal: Diabetes Care (2023)

OBJECTIVE Car dependency contributes to physical inactivity and, consequently, may increase the likelihood of diabetes. We investigated whether neighborhoods that are highly conducive to driving confer a greater risk of developing diabetes and, if so, whether this differs by age. RESEARCH DESIGN AND METHODS We used administrative health care data to identify all working-age Canadian adults (20–64 years) who were living in Toronto on 1 April 2011 without diabetes (type 1 or 2). Neighborhood drivability scores were assigned using a novel, validated index that predicts driving patterns based on built environment features divided into quintiles. Cox regression was used to examine the association between neighborhood drivability and 7-year risk of diabetes onset, overall and by age-group, adjusting for baseline characteristics and comorbidities. RESULTS Overall, there were 1,473,994 adults in the cohort (mean age 40.9 ± 12.2 years), among whom 77,835 developed diabetes during follow-up. Those living in the most drivable neighborhoods (quintile 5) had a 41% higher risk of developing diabetes compared with those in the least drivable neighborhoods (adjusted hazard ratio 1.41, 95% CI 1.37–1.44), with the strongest associations in younger adults aged 20–34 years (1.57, 95% CI 1.47–1.68, P &amp;lt; 0.001 for interaction). The same comparison in older adults (55–64 years) yielded smaller differences (1.31, 95% CI 1.26–1.36). Associations appeared to be strongest in middle-income neighborhoods for younger residents (middle income 1.96, 95% CI 1.64–2.33) and older residents (1.46, 95% CI 1.32–1.62). CONCLUSIONS High neighborhood drivability is a risk factor for diabetes, particularly in younger adults. This finding has important implications for future urban design policies.
Should a Systematic Review Be Required in a Clinical Trial Report? Perhaps, But Not Yet
Authors: Ivo Abraham, Matthias Calamia, Karen MacDonald
Journal: JAMA Network Open (2023)

Yuanxi Jia, PhD; Bingli Li, MDS; Zhirong Yang, PhD; Fuxiao Li, PhD; Ziyi Zhao, MPH; Chang Wei, ScM; Xuhao Yang, MSPH; Qianyi Jin, BSCI; Di Liu, PhD; Xin Wei, MD; Jennifer Yost, PhD; Hans Lund, PhD; Jinling Tang, PhD; Karen A. Robinson, PhD
G-CSF Is a Novel Mediator of T-Cell Suppression and an Immunotherapeutic Target for Women with Colon Cancer
Authors: Anita L. Ray, Apryl S. Saunders, Robert A. Nofchissey, Megan A. Reidy, Maria Kamal, Megan R. Lerner, Kar-Ming Fung, Mark L. Lang, Joshua A. Hanson, Shaoxuan Guo, Maria G. Urdaneta-Perez, Samara E. Lewis, Michael Cloyde, Katherine T. Morris
Journal: Clinical Cancer Research (2023)

G-CSF enhances colon cancer development. This study defines the prevalence and effects of increased G-CSF signaling in human colon cancers and investigates G-CSF inhibition as an immunotherapeutic strategy against metastatic colon cancer.Patient samples were used to evaluate G-CSF and G-CSF receptor (G-CSFR) levels by IHC with sera used to measure G-CSF levels. Peripheral blood mononuclear cells were used to assess the rate of G-CSFR+ T cells and IFNγ responses to chronic ex vivo G-CSF. An immunocompetent mouse model of peritoneal metastasis (MC38 cells in C57Bl/6J) was used to determine the effects of G-CSF inhibition (αG-CSF) on survival and the tumor microenvironment (TME) with flow and mass cytometry.In human colon cancer samples, the levels of G-CSF and G-CSFR are higher compared to normal colon tissues from the same patient. High patient serum G-CSF is associated with increases in markers of poor prognosis, (e.g., VEGF, IL6). Circulating T cells from patients express G-CSFR at double the rate of T cells from controls. Prolonged G-CSF exposure decreases T cell IFNγ production. Treatment with αG-CSF shifts both the adaptive and innate compartments of the TME and increases survival (HR, 0.46; P = 0.0237) and tumor T-cell infiltration, activity, and IFNγ response with greater effects in female mice. There is a negative correlation between serum G-CSF levels and tumor-infiltrating T cells in patient samples from women.These findings support G-CSF as an immunotherapeutic target against colon cancer with greater potential benefit in women.
Mpox outbreak in the Netherlands, 2022: public health response, characteristics of the first 1,000 cases and protection of the first-generation smallpox vaccine
Authors: Catharina E van Ewijk, Fuminari Miura, Gini van Rijckevorsel, Henry JC de Vries, Matthijs RA Welkers, Oda E van den Berg, Ingrid HM Friesema, Patrick R van den Berg, Thomas Dalhuisen, Jacco Wallinga, Diederik Brandwagt, Brigitte AGL van Cleef, Harry Vennema, Bettie Voordouw, Marion Koopmans, Annemiek A van der Eijk, Corien M Swaan, Margreet JM te Wierik, Tjalling Leenstra, Eline Op de Coul, Eelco Franz
Journal: Eurosurveillance (2023)

In early May 2022, a global outbreak of mpox started among persons without travel history to regions known to be enzootic for monkeypox virus (MPXV). On 8 August 2022, the Netherlands reported its 1,000th mpox case, representing a cumulative incidence of 55 per million population, one of the highest cumulative incidences worldwide. We describe characteristics of the first 1,000 mpox cases in the Netherlands, reported between 20 May and 8 August 2022, within the context of the public health response. These cases were predominantly men who have sex with men aged 31–45 years. The vast majority of infections were acquired through sexual contact with casual partners in private or recreational settings including LGBTQIA+ venues in the Netherlands. This indicates that, although some larger upsurges occurred from point-source and/or travel-related events, the outbreak was mainly characterised by sustained transmission within the Netherlands. In addition, we estimated the protective effect of first-generation smallpox vaccine against moderate/severe mpox and found a vaccine effectiveness of 58% (95% CI: 17–78%), suggesting moderate protection against moderate/severe mpox symptoms on top of any possible protection by this vaccine against MPXV infection and disease. Communication with and supporting the at-risk population in following mitigation measures remains essential.
The Cellular Landscape of Chronic Thromboembolic Pulmonary Hypertension Revealed by Single-Cell Sequencing: Therapeutic Implications?
Authors: Rozenn Quarck, Harm Jan Bogaard, Marion Delcroix
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"The Cellular Landscape of CTEPH Revealed by Single Cell Sequencing: Therapeutic Implications?." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp. –
Treatment With Liposomal Irinotecan Plus Fluorouracil and Leucovorin for Patients With Previously Treated Metastatic Biliary Tract Cancer
Authors: Jaewon Hyung, Ilhwan Kim, Kyu-pyo Kim, Baek-Yeol Ryoo, Jae Ho Jeong, Myoung Joo Kang, Jaekyung Cheon, Byung Woog Kang, Hyewon Ryu, Ji Sung Lee, Kyung Won Kim, Ghassan K. Abou-Alfa, Changhoon Yoo
Journal: JAMA Oncology (2023)

Importance The NIFTY trial demonstrated the benefit of treatment with second-line liposomal irinotecan (nal-IRI) plus fluorouracil (FU) and leucovorin (LV) for patients with advanced biliary tract cancer (BTC). Objective To report the updated efficacy outcomes from the NIFTY trial with extended follow-up of 1.3 years with reperformed masked independent central review (MICR) with 3 newly invited radiologists. Design, Setting, and Participants The NIFTY trial was a randomized, multicenter, open-label, phase 2b clinical trial conducted between September 5, 2018, and December 31, 2021, at 5 tertiary referral centers in South Korea. Patients with advanced BTC whose disease progressed while receiving first-line gemcitabine plus cisplatin with at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors, version 1.1, were eligible. Data analysis was completed on May 9, 2022. Interventions Patients were randomized 1:1 to receive LV, 400 mg/m 2 , bolus and FU, 2400 mg/m 2 , for a 46-hour infusion intravenously every 2 weeks with or without nal-IRI, 70 mg/m 2 , before LV intravenously. Patients were treated until disease progression or unacceptable toxic effects. Main Outcomes and Measures Primary end point was progression-free survival (PFS) as assessed by MICR. Secondary end points were PFS as assessed by the investigator, overall survival, and objective response rate. Results A total of 178 patients (75 women [42.1%]; median [IQR] age, 64 [38-84] years) were randomly assigned, and 174 patients were included in the full analysis set (88 patients [50.6%] in the nal-IRI plus FU/LV group vs 86 patients [49.4%] in the FU/LV alone group). In this updated analysis, the median MICR-assessed PFS was 4.2 months (95% CI, 2.8-5.3) for the nal-IRI plus FU/LV group and 1.7 months (95% CI, 1.4-2.6) for the FU/LV alone group (hazard ratio, 0.61; 95% CI, 0.44-0.86; P = .004), in contrast to the 7.1 and 1.4 months reported in the previous study, respectively. The discordance rate for tumor progression date between the MICR and investigators was 17.8% (vs 30% in the previous study). Conclusions and Relevance The NIFTY randomized clinical trial demonstrated significant improvement in PFS with treatment with nal-IRI plus FU/LV compared with FU/LV alone for patients with advanced BTC after progression to gemcitabine plus cisplatin. The combination of nal-IRI plus FU/LV could be considered as a second-line treatment option for patients with previously treated advanced BTC. Trial Registration clinicaltrials.gov Identifier: NCT03524508
Stromal and therapy-induced macrophage proliferation promotes PDAC progression and susceptibility to innate immunotherapy
Authors: Chong Zuo, John M. Baer, Brett L. Knolhoff, Jad I. Belle, Xiuting Liu, Angela Alarcon De La Lastra, Christina Fu, Graham D. Hogg, Natalie L. Kingston, Marcus A. Breden, Paarth B. Dodhiawala, Daniel Cui Zhou, Varintra E. Lander, C. Alston James, Li Ding, Kian-Huat Lim, Ryan C. Fields, William G. Hawkins, Jason D. Weber, Guoyan Zhao, David G. DeNardo
Journal: The Journal of Experimental Medicine (2023)

Tumor-associated macrophages (TAMs) are abundant in pancreatic ductal adenocarcinomas (PDACs). While TAMs are known to proliferate in cancer tissues, the impact of this on macrophage phenotype and disease progression is poorly understood. We showed that in PDAC, proliferation of TAMs could be driven by colony stimulating factor-1 (CSF1) produced by cancer-associated fibroblasts. CSF1 induced high levels of p21 in macrophages, which regulated both TAM proliferation and phenotype. TAMs in human and mouse PDACs with high levels of p21 had more inflammatory and immunosuppressive phenotypes. p21 expression in TAMs was induced by both stromal interaction and/or chemotherapy treatment. Finally, by modeling p21 expression levels in TAMs, we found that p21-driven macrophage immunosuppression in vivo drove tumor progression. Serendipitously, the same p21-driven pathways that drive tumor progression also drove response to CD40 agonist. These data suggest that stromal or therapy-induced regulation of cell cycle machinery can regulate both macrophage-mediated immune suppression and susceptibility to innate immunotherapy.
Efficacy of Alternative Dose Regimens of Exemestane in Postmenopausal Women With Stage 0 to II Estrogen Receptor–Positive Breast Cancer
Authors: Davide Serrano, Sara Gandini, Parjhitham Thomas, Katherine D. Crew, Nagi B. Kumar, Lana A. Vornik, J. Jack Lee, Paolo Veronesi, Giuseppe Viale, Aliana Guerrieri-Gonzaga, Matteo Lazzeroni, Harriet Johansson, Mauro D’Amico, Flavio Guasone, Stefano Spinaci, Bjørn-Erik Bertelsen, Gunnar Mellgren, Isabelle Bedrosian, Diane Weber, Tawana Castile, Eileen Dimond, Brandy M. Heckman-Stoddard, Eva Szabo, Powel H. Brown, Andrea DeCensi, Bernardo Bonanni
Journal: JAMA Oncology (2023)

Successful therapeutic cancer prevention requires definition of the minimal effective dose. Aromatase inhibitors decrease breast cancer incidence in high-risk women, but use in prevention and compliance in adjuvant settings are hampered by adverse events.
Metastatic Crohn disease improving with vedolizumab
Authors: Marta Costa Blasco, Orla McFeely, Claire  Doyle, Anna Wolinska, Madonna  Andrawis, Lisa  Murphy, Paula Beatty, Sarah O’Mahony, Caitriona  Hackett
Journal: British Journal of Dermatology (2023)

Metastatic Crohn disease responding to vedolizumab.
Dendritic cell subsets in cancer immunity and tumor antigen sensing
Authors: Annalisa Del Prete, Valentina Salvi, Alessandra Soriani, Mattia Laffranchi, Francesca Sozio, Daniela Bosisio, Silvano Sozzani
Journal: Cellular and Molecular Immunology (2023)

Abstract Dendritic cells (DCs) exhibit a specialized antigen-presenting function and play crucial roles in both innate and adaptive immune responses. Due to their ability to cross-present tumor cell-associated antigens to naïve T cells, DCs are instrumental in the generation of specific T-cell-mediated antitumor effector responses in the control of tumor growth and tumor cell dissemination. Within an immunosuppressive tumor microenvironment, DC antitumor functions can, however, be severely impaired. In this review, we focus on the mechanisms of DC capture and activation by tumor cell antigens and the role of the tumor microenvironment in shaping DC functions, taking advantage of recent studies showing the phenotype acquisition, transcriptional state and functional programs revealed by scRNA-seq analysis. The therapeutic potential of DC-mediated tumor antigen sensing in priming antitumor immunity is also discussed.